The following is intended to provide guidance for going
about determining the economics of using a pasteurellae (Mannheimia now) vaccine
in calves, the question that came from the class discussion.

Please work in groups of several students each - multiple minds are
better than one and it spreads the work around.

Task:

Frame the question well that you wish to answer.

For example: "Does the evidence show that using <vaccine X> at <timing> in
<livestock class> under my client's circumstances is economically
beneficial?"

In this case, we discussed the using the vaccine pre-weaning in
calves that your client was going to ship to a feedlot and retain
ownership. Hence, the client is interested in the economic benefit from
reduced morbidity and mortality during weaning on the ranch and after
being shipped to the feedyard.

Pick the product; there are a number available that have a label claim against
Mannheimia hemolytica (e.g., Boehringer
Ingelheim Express 5-PHM, Pfizer "One Shot" (is it really only one shot? read
the label closely), Fort Dodge Presponse, Intervet Vista Once SQ, and so on)
but they differ. (Hint: vaccines under different brand names but having the
same veterinary license number are effectively identical vaccines).

What is the evidence? Search for the evidence - primary
literature papers, meeting proceedings, manufactures technical literature,
extension publications. The following is one approach:

Search the on-line databases, such as
PubMed.
At WSU, go to the
Database Index.
(accessing PubMed or Web of Science through enables you to print out the
article PDF if WSU has rights to it)

Try the following for a very powerful trace through the
literature (not available outside WSU, unfortunately, while PubMed is):

On the WSU
Database
Index, select "Databases A to Z" and type in "Web of Science".

Click on "Web of Science". Click on "Web of Science" again.
Click on "General Search".

Enter the search terms you have come up with ("mannheimia bovine
bacterin efficacy" (no quotes) brings up 1 paper).

Click on the "Find @ WSU" button.

Click on the "Go" button and you reading the paper.

Go back to the Web of Science page and click on "Times Cited" -
that brings up the citation of every newer paper that cited this paper.

Using this on older but key papers works well because
authors writing newer papers in the area will often cite
such papers

Go back to the Web of Science page and click on "Cited
References" - now you have links to most of the cited papers and you
can do the same process with them (note the Shewen and Wilkie paper
- one of the early, key leucotoxin papers).

This is a great way to identify the important older
papers; key older papers will often have a lot of citations

If you with all that haven't located good papers with the answer to
your question, Google around for other stuff, such as extension publications.

Note the TexVAC program listed below, a google hit.

Other things you could try:

Go to your list of experts, search the AABP-L archives, post a
question, call the company and so on

Watch the trade magazines; they often provide links to good
information resources

Consider analogical evidence from similar systems with a similar
problem. For example, pneumonic pasteurellosis is a major problem in
dairy calves, which are often under more severe challenge than beef
calves.

Note: The two papers I was thinking of are by BD Hunsaker (no "c") but the
only way to access them online is through the AABP website (Bovine Practitioner,
January '97, and the 2007 Proceedings). Neither appears in PubMed or Web
of Science.

What is the strength of this evidence? A critical step is
evaluating the studies! Select the best evidence to apply to your client's
herd.

Sufficient strong evidence? Answer "yes" or "no" and why so
or why not. Commit yourself in writing, if you dare. Recall that "The
faintest pencil is stronger than the strongest mind" and "Success has
many fathers but failure is an orphan". If you want credit in the
future, write it down.

Provide the search strings for the databases you used or otherwise
describe how you found any papers you used (good sets of terms and using
them well are key to successful searching)

Vaccination Programs:

(modified from a
presentation to livestock producers)

One size does not fit all!

Establishing a vaccination program for a herd requires consideration
of complex issues. To quote Brand et al. (1996): "A vaccination program must be based
on the disease status of the herd, reproductive status of youngstock and cows, potential
interference by maternally derived antibodies, potential effects of vaccine-induced titers
on suitability for export or introduction into bull studs, whether the herd is open or
closed, prevailing farm and area conditions, national or regional vaccination strategies,
the possible advantageous/disadvantageous post-vaccination sequalae, and the cost
benefit ratio of a vaccination program (emphasis mine). Furthermore, the vaccination
schedule should be known, as well as the antigenic form of vaccine to be used
(inactivated, modified live, live, or deletion vaccine), route of administration
(intramuscularly, subcutaneously, or intranasally), and whether a booster vaccination is
needed and when." Because the immune system requires time to respond to vaccines, the
final dose should be given sufficiently in advance that the animal can be fully protected
when the exposure or stress occurs. Vaccines requiring priming doses must be given
sufficiently ahead of the second dose for the second dose to stimulate adequate
protection. Failure to follow the administration instructions in this regard is a common
error that markedly reduces vaccine efficacy.

Many vaccines are likely only marginally beneficial, biological and
economically.

Some vaccines, such as the oil adjuvant vibrio (Campylobacter fetus)
and the muscle clostridial toxoids (e.g., Clostridium chauvoei (blackleg), Cl.
Septicum (malignant edema)), are highly efficacious. At the other end of the spectrum
are the older Pasteurella whole cell bacterins that don't contain leucotoxoids as
some evidence suggests that they actually increase the severity of bovine respiratory
disease under some circumstances. Others fall in between. For example, a controlled study
of the trichomoniasis vaccine showed that 63% of vaccinated heifers delivered calves while
only 32% of the controls did so and the vaccinates were culture positive for 3.8 weeks
while controls were for 5.4 weeks (Kvasnicka Am J Vet Res 53:2023(1992)). Although
the vaccine improved the situation, it certainly didn't prevent the problem. Other control
measures such as rigorous testing of young bulls, culling of older bulls and late calvers
may be more beneficial economically. Some vaccines such as leptospirosis
are considerably more effective against non-host adapted strains than host-adapted
strains. A general rule of thumb is that if a natural infection after birth results in a
chronic carrier animal, which means that that animal's immune system was not able to
eliminate the infection, then vaccination of that animal isn't going to stimulate the
immune system sufficiently to prevent infection either. Thus, a general conclusion is that
many vaccines will reduce the number of animals infected, will reduce the proportion of
those that become clinical cases among those that are infected and will reduce the amount
and duration of shedding in those that are infected. But for many diseases
vaccination will not completely prevent the problem and other control measures may be
equally or more important. Unfortunately, it is human nature to look for the single magic
bullet that can be given once and forgotten.

The evidence from sound studies of a positive economic benefit from the
use of many vaccines across large numbers of herds is lacking. The lack of sound
evidence doesn't necessarily mean that the cost-benefit isn't positive. Anecdotal evidence
suggests that the severe clinical outbreaks of Type II BVD tended to occur in herds that
were not properly vaccinated for BVD. For bovine respiratory disease, about half of the
studies indicate equivocal benefit while half indicate marginal benefit of use in calves
prior to weaning. As noted in the pneumonia example above, their use clearly doesn't
completely prevent the problem. To get the needed evidence of benefit, producers need to
make the evidence from sound randomized, multi-herd, concurrent controlled, blinded field
trials a condition of purchase.

USDA vaccine licensing does not require evidence of efficacy in
cattle under normal farm and ranch conditions and only requires evidence of
efficacy against specific aspects of the disease.

The USDA provides minimal monitoring of vaccines for safety, purity,
potency and efficacy, concentrating primarily on safety and purity (freedom from other
infectious agents or toxic materials). This is done by monitoring the procedures and
sanitation in the plants producing the product. To show efficacy of vaccines the
manufacturer performs laboratory challenge of specially selected animals rather than using
controlled field studies of vaccine efficacy under actual use conditions. In the Espeseth
and Greenberg document on the "Published Articles" website referenced below, it
states "It is generally more difficult to demonstrate significant efficacy under
field conditions. Field efficacy studies are often inconclusive because of uncontrollable
outside influences." Further, if other sound, independent evidence shows that a
USDA-approved product is not efficacious under most circumstances, the law does not
prevent its production or sale. Thus, a USDA-approved and licensed product may not be
efficacious under the under field conditions.
Further, the aspect of the disease against which efficacy must be demonstrated
is quite specific. For example, for the BVD vaccines evidence of efficacy
against the clinical gastointestinal disease syndrome is required but efficacy
against fetal infection, which is essential for preventing the persistent
carrier state and the most important component for control of BVD in breeding
herds, is not unless it is a specific label claim.

My recommendation is that in concert with their herd veterinarian,
producers design a vaccination program for the specific circumstances of their herd.
Without knowledge of the herd specifics and of the area I'm unwilling to make blanket
recommendations. I also suggest that producers put their vaccine requirements out to bid.
With the
above caveats in mind, the following are on-line vaccine recommendations in title
alphabetical order from a number of experts:

The Iceberg Principle:
With most diseases in a herd, more subclinical
(silent) cases occur than clinical cases.

Even in outbreak situations more animals in the
affected group have infections and are subclinical or silent cases than
there are clinical cases. For most diseases, both infectious and
non-infectious, the ratio between clinical cases and subclinical cases
is typically 1:5 to 1:20. Under some circumstances, a herd can be widely
infected with an infectious agent but few if any clinical cases occur at
all. For some infections such as Bovine Leukemia Virus (BLV) the ratio
may be 1:100, meaning that clinical cases rarely occur. Many clinical cases are due to infectious agents that are in most
herds most of the time but that usually don't cause clinical disease. Thus, the occurrence
of clinical cases is an indicator that something is amiss in the management of those
animals.

Good explanations of the balance between resistance and disease
challenge and fitting these into the beef cow production cycle are those
authored by Dr. Ed J.
Richey, Univ of Florida Beef Extension veterinarian:

Because subclinical (silent) cases of most diseases are more
numerous than clinical cases in a herd, the economic cost of subclinical disease exceeds
that of clinical disease.

New infectious agents often enter a herd and are unnoticed for some
time before clinical disease occurs and a diagnosis is finally made.

Carriers of subclinical infection are the reason for the old but
true saying that "Most disease is bought and paid for!" and are what keep
it in a herd.

Quarantine isolation of purchased animals will not protect
a herd against the chronic carriers of many infectious agents!

Even using the best laboratory tests, subclinical (silent) disease
is considerably harder to detect and diagnose than is clinical disease and is more
error-prone.

For many infectious diseases, the single most important piece of
information that a purchaser can have is honest, sound knowledge about the status of the
herd of origin with respect to the infections of concern.

Work with rather than against "Mother Nature":

Taking advantage of the opportunities that Mother
Nature presents is far less costly and more effective than fighting Mother Nature, which
is often a loosing battle.

Continued success is far more likely if a disease problem is
attacked at multiple points rather than attacking it at a single control point.

For example of management practices to reduce calf scours, Prevention of neonatal calf diarrhea with the Sandhills Calving System (Dr. David Smith, U Nebraska,
pdf)

Other On-line Information Sources:

The Internet contains a wealth of relevant materials, one
reason being that a major mission of the agricultural extension service is
to communicate information to producers. The Internet provides an excellent
mechanism for doing so to the dispersed producer audience. As a result, many
very useful extension publications are on the Web. The medical literature
can also be searched for free on-line through the National Library of
Medicine. Cornell Consultant also provides an on-line means of identifying
the most recent relevant clinical literature as selected by Dr. Maurice
White, a Cornell food animal clinician.